Abstract
Immune checkpoints expressed on tumor cells may suppress the cytotoxicity of tumor-infiltrating lymphocytes (TILs) via interaction with their ligands. In the present study, checkpoint proteins and ligands, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cluster of differentiation (CD)155 and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) were systematically analyzed in patients with small cell lung cancer (SCLC). Furthermore their clinicopathological features and survival rates were investigated. Immunohistochemistry was performed in order to analyze the expression of PD-L1, CD155, PD-1 and TIGIT in 60 patients with SCLC, and survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. It was reported that CD155/TIGIT and PD-L1/PD-1 were highly expressed on tissues of surgically resected SCLC. High expression levels of PD-L1, CD155 or PD-L1+CD155 were significantly associated with shorter survival. However, high expression levels of PD-1 or TIGIT exhibited no obvious association with shorter survival time. Moreover, patients with SCLC in whom PD-L1 and CD155 levels were highly expressed had the shortest survival rate. Multivariate survival analysis revealed that highly expressed PD-L1 [hazard ratio (HR)=2.55, 95% confidence interval (CI)=1.18-5.51, P=0.017] and CD155 (HR=2.40, 95% CI=1.05-5.50, P=0.038) were independent prognostic factors for overall survival (OS) time in SCLC. In addition, it was reported that TIGIT and PD-1, the receptors of CD155 and PD-L1, respectively, were also constitutively expressed on CD8+ TILs and tumor cells in SCLC. High expression levels of PD-L1 and CD155 were independent prognostic factors for OS time in patients with SCLC.